Angiogenesis, formation of new blood vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis (and shrinking tumors through nutrient starvation) hold great promise in cancer treatment because they avoid major problems associated with standard chemo or radiotherapy, i.e., the eventual growth of tumors resistant to the therapeutic agent, the debilitating systemic side effects engendered by chemotherapy, and the generation of secondary cancers by radiotherapy. The generation of biological agents that specifically suppress the angiogenic activity of tumor-promoting factors in the body is potentially an excellent means of creating novel cancer therapy agents. The specific aims of Phase I of this application are 1) to generate and purify monoclonal antibodies directed against a particular angiogenic factor that is strongly implicated as an essential regulator of tumor growth, and 2) to screen these antibodies in animals for their ability to block the activity of the targeted factor. In Phase II, antibodies identified as suppressors of the targeted factor's tumor growth-promoting activity would be adapted for clinical use as cancer therapeutic agents. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of mortality in the U.S., and its health care costs are well over $100 billion. Solid tumors comprise the majority of cancers, afflict over 3 million people, and cause over a half million deaths annually. The health care market for anti- angiogenesis anti-cancer agents in very significant because conventional cancer therapy often results in resistant cancer cells, and causes serious side effects. COLLABORATING INSTITUTIONS: